nitroarginine and Hemorrhage

Topics: Anemia; Animals; Arginine; Bleeding Time; Blood Platelets; Endothelium, Vascular; Enzyme Inhibitors; Erythropoietin; Guanidines; Hemorrhage; History, 18th Century; History, 20th Century; Humans; Isoenzymes; Kidney Failure, Chronic; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; omega-N-Methylarginine; Rats; Succinates; Uremia

The possible involvement of the L-arginine-nitric oxide pathway and endogenous opioid mechanisms in the hemorrhagic hypotension- (HH) induced changes of hepatic arterial blood flow and vascular resistance was studied in cats. During HH hepatic arterial blood flow was significantly higher both in L-arginine- and naloxone-treated animals than in controls. Furthermore, HH induced a significant increase of the hepatic vascular resistance in the control group, which was prevented by L-arginine or naloxone treatment. Because inhibition of the nitric oxide synthesis by N(G)-nitro-L-arginine in normotensive cats induced a similar increase of the hepatic vascular resistance to that observed during HH in the control group, our results indicate that impairment of the endothelial function may be responsible for the hemorrhage-induced L-arginine- and naloxone-reversible hepatic arterial vasoconstriction. This hypothesis is consistent with our previous observations demonstrating the development of endothelial dysfunction in the feline hepatic artery during HH.

Topics: Animals; Arginine; Cats; Drug Evaluation, Preclinical; Hemorrhage; Hypotension; Liver; Male; Naloxone; Nitroarginine; Regional Blood Flow; Vasoconstriction

Our earlier studies have shown development of endothelial dysfunction in the feline renal artery during hemorrhagic hypotension. Because L-arginine (L-Arg), the precursor of nitric oxide (NO), reportedly improves endothelial function in several pathophysiological states including hypotension, we investigated its possible beneficial effect on the adrenal and renal circulations during hemorrhagic hypotension in anesthetized, ventilated cats. Hypotension (mean arterial pressure 50 mm Hg) significantly increased vascular resistance and decreased blood flow (radiolabeled microspheres) in both adrenal and renal cortices. L-Arg (30 mg/kg bolus, 10 mg/kg/min infusion, i.v.) had no significant hemodynamic effects in normotension but prevented the increase of the vascular resistance and improved blood flow in the adrenal cortex during hypotension. In the kidney, L-Arg also prevented hemorrhage-induced vasoconstriction, although its effect on blood flow did not reach significance. The NO synthase inhibitor N(G)-nitro-L-arginine (30 mg/kg bolus, 1 mg/kg/min infusion, i.v.) increased adrenal and renal vascular resistances to a similar extent as that observed during hypotension. It thus seems that an L-Arg-reversible dysfunction of the endothelial NO-synthesizing pathway contributes to hemorrhage-induced adrenal and renal vasoconstriction.

Topics: Adrenal Glands; Animals; Cats; Hemorrhage; Hypotension; Kidney; Male; Nitroarginine; Renal Circulation; Vasoconstriction

Viscoelastic and electrophysiological mechanisms have been implicated in resetting of baroreceptors in hypertension, but resetting in response to hypotension has been less exhaustively studied. To assess the importance of viscoelastic mechanisms in hypotension, we examined the behavior of the "in situ" aorta during hemorrhage. Fifteen minutes of hemorrhage in anesthetized Wistar rats produced stable hypotension (30 mmHg) and a progressive contraction of the mean aortic caliber (-93.8 +/- 18.0 microns, P < 0.05) compared with control measurements. Contraction was not altered by sinoaortic denervation, vagotomy, nephrectomy, adrenalectomy, hexamethonium (30 mg/kg), losartan (10 mg/kg), V1 antagonist (10 micrograms/kg), arterial pH and blood gas control, or indomethacin (3.0 mg/kg). Aortic contraction was greater in rats treated with N omega-nitro-L-arginine (-164.0 +/- 43.0 microns, P < 0.05) than in those treated with sodium nitroprusside (-54.1 +/- 7.5 microns, P < 0.05). The results indicate that aortic contraction is compatible with viscoelastic contraction and suggest that shortening of viscoelastic elements in series with baroreceptor endings increases stress at the baroreceptor membrane and contributes to the development of baroreceptor resetting to hypotension.

Topics: Animals; Aorta; Arginine; Blood Pressure; Elasticity; Gases; Hemorrhage; Hydrogen-Ion Concentration; Hypotension; Indomethacin; Male; Nitroarginine; Nitroprusside; Rats; Rats, Wistar; Viscosity

Topics: Acetylcholine; Adenosine Triphosphate; Amino Acid Oxidoreductases; Analgesics; Animals; Arginine; Blood Pressure; Blood Transfusion; Brain; Cats; Cerebral Arteries; Cerebral Cortex; Cerebrovascular Circulation; Electroencephalography; Hemorrhage; Hypotension; Indazoles; Male; Molsidomine; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Norepinephrine; Organ Specificity; Parietal Lobe; Pituitary Gland; Regional Blood Flow; Spinal Cord; Vasodilator Agents

Endothelium-derived relaxing factor (EDRF) is a potent vasodilator, and is also, in vitro, a platelet-inhibitor. Experiments were performed to determine whether systemically released EDRF inhibits platelet-dependent hemostasis in vivo. Rabbits were treated with agents to release or block EDRF, and 5 standardized incisions were made in the ear. Carbachol, infused to stimulate EDRF release, abruptly lowered the blood pressure and caused increased bleeding. Neither effect was attributable to prostacyclin since neither was blocked by treatment of the rabbits with acetylsalicylic acid. In contrast, both the hypotension and bleeding were attenuated by the selective antagonist of EDRF synthesis, NG-nitro-L-arginine. However, neither the hypotension nor the bleeding associated with carbachol was inhibited by an infusion of free hemoglobin, used to scavenge intraluminally-released EDRF. We conclude that in this model endogenously-released EDRF increases bleeding indirectly by provoking vasodilatation, rather than directly by inhibiting platelet function.

Topics: Animals; Arginine; Blood Platelets; Blood Pressure; Carbachol; Female; Hemoglobins; Hemorrhage; Hemostasis; Male; Nitric Oxide; Nitroarginine; Rabbits; Statistics as Topic